Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation.

Both nonneoplastic colon epithelium and colon carcinoma cells in situ are continuously exposed to lipopolysaccharide (LPS). Few reports have addressed possible direct effects of LPS in promotion of colon carcinoma and underlying mechanisms. We found evidence that LPS directly stimulated growth of the human colon carcinoma cell line CE-1 through an increase in the production of prostaglandin E₂ (PGE₂) as a result of cyclo-oxygenase-2 (COX-2) expression. LPS induced significant increases in PGE₂ production in CE-1 cells, which were found to express a high-affinity LPS receptor, CD14. Positive correlations were found between PGE₂ production and activation of nuclear factor (NF)-κB as well as expression of both COX-2 mRNA and protein in LPS-stimulated CE-1 cells. When CE-1 cells were exposed to exogenous PGE₂, DNA synthesis increased. These results indicate that LPS may stimulate DNA synthesis in certain colon carcinoma cells as a result of PGE₂ production involving increased COX-2 expression that might result in turn from activation of NF-κB by LPS. Further investigation of the pathways mediating LPS-induced stimulation of colon carcinoma cells may provide insights into LPS effects in in vivo tumor biology. Oncogene (2000) 19, 1225–1231. [ABSTRACT FROM AUTHOR]